Efficacy and Safety Study of Apixaban for the Treatment of Deep Vein Thrombosis or Pulmonary Embolism

Venous Thrombosis Clinical Trial

Official title:

A Safety and Efficacy Trial Evaluating the Use of Apixaban in the Treatment of Symptomatic Deep Vein Thrombosis and Pulmonary Embolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00643201
• Other study ID #: CV185-056
• Secondary ID: EUDRACT: 2007-00
• Status: Completed
• Phase: Phase 3
• First received: March 20, 2008
• Last updated: April 17, 2014
• Start date: July 2008
• Est. completion date: March 2013

Study information

• Verified date: April 2014
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug AdministrationCanada: Health CanadaArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBrazil: National Health Surveillance AgencyChile: Instituto de Salud Pública de ChileMexico: Federal Commission for Sanitary Risks ProtectionAustria: Secretariat of HealthDenmark: Danish Medicines AgencyFrance: Ministry of HealthGermany: Ministry of HealthIsrael: Ministry of HealthItaly: Ministry of HealthNorway: Directorate of HealthSpain: Spanish Agency of MedicinesSouth Africa: Department of HealthTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyCzech Republic: Ministry of HealthHungary: Ministry of Health, Social and Family AffairsPoland: Ministry of HealthRussia: Ministry of Health of the Russian FederationUkraine: Ministry of HealthAustralia: Department of Health and Ageing Therapeutic Goods AdministrationHong Kong: Department of HealthIndia: Central Drugs Standard Control OrganizationKorea: Food and Drug AdministrationMalaysia: National Pharmaceutical Control BureauTaiwan: Department of HealthRomania: National Medicines AgencyPortugal: National Pharmacy and Medicines InstituteSingapore: Ministry of HealthChina: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effects of an investigational blood thinner, apixaban, in preventing venous thromboembolic (VTE) recurrence or death in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5614
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men and women = 18 years of age

• Clinical diagnosis of DVT or PE

Exclusion Criteria:

• Contraindications for enoxaparin or warfarin

• Active bleeding or high risk for serious bleeding

• Short life expectancy

• Uncontrolled high blood pressure

• Significantly impaired kidney or liver function

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pulmonary Embolism
• Thrombosis
• Venous Thrombosis

Intervention

Drug:
• Enoxaparin
solution, subcutaneous, 1 mg/kg Q12h until International normalized ratio (INR) =2.
• warfarin
tablets, oral, dosing to target INR range between 2.0 - 3.0, once daily, 6 months
• Placebo for apixaban
tablets, oral, 10 mg tablets, twice daily, for 7 days followed by placebo for apixaban 5 mg tablets, twice daily, 6 months
• Placebo for enoxaparin
solution, subcutaneous, 1 mg/kg Q12h until sham INR =2.
• Placebo for warfarin
tablets, oral, dosing to target sham INR range between 2.0 - 3.0, once daily, 6 months
• apixaban
tablets, oral, 10 mg tablets, twice daily, for 7 days followed by apixaban 5 mg, twice daily, 6 months

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Ciudad Autonoma De Buenos Aire	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Corrientes
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	Rosario	Santa Fe
Australia	Local Institution	Adelaide	South Australia
Australia	Local Institution	Bedford Park	South Australia
Australia	Local Institution	Box Hill	Victoria
Australia	Local Institution	Clayton	Victoria
Australia	Local Institution	Concord	New South Wales
Australia	Local Institution	Garran	Australian Capital Territory
Australia	Local Institution	Herston	Queensland
Australia	Local Institution	Hobart	Tasmania
Australia	Local Institution	Kogarah	New South Wales
Australia	Local Institution	Lismore	New South Wales
Australia	Local Institution	Perth	Western Australia
Australia	Local Institution	Randwick	New South Wales
Australia	Local Institution	Ringwood East	Victoria
Australia	Local Institution	Windsor	Victoria
Austria	Local Institution	Graz
Austria	Local Institution	Innsbruck
Austria	Local Institution	Vienna
Austria	Local Institution	Vienna
Austria	Local Institution	Vienna
Austria	Local Institution	Vienna
Austria	Local Institution	Wien
Brazil	Local Institution	Belo Horizonte - Mg	Minas Gerais
Brazil	Local Institution	Botucatu	Sao Paulo
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Liberdade	Sao Paulo
Brazil	Local Institution	Port Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Rio Janeiro	Rio De Janeiro
Brazil	Local Institution	Sao Bernardo do Campo	SP
Brazil	Local Institution	Sao Jose Do Rio Preto	Sao Paulo
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Greenfield Park	Quebec
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Ottawa	Ontario
Canada	Local Institution	Saint John	New Brunswick
Canada	Local Institution	St. Jerome	Quebec
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Vancouver	British Columbia
Canada	Local Institution	Vancouver	British Columbia
Canada	Local Institution	Victoria	British Columbia
Canada	Local Institution	Waterloo	Ontario
Canada	Local Institution	Windsor	Ontario
Canada	Local Institution	Winnipeg	Manitoba
Chile	Local Institution	Independencia	Metropolitana
Chile	Local Institution	Punta Arenas	Magallanes Antartica
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Vina Del Mar	Valparaiso
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Beijing	Beijing
China	Local Institution	Guangzhou	Guangdong
China	Local Institution	Hangzhou	Zhejiang
China	Local Institution	Hangzhou	Zhejiang
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shanghai	Shanghai
China	Local Institution	Shengyang	Liaoning
China	Local Institution	Wuhan	Hubei
China	Local Institution	Xian
Czech Republic	Local Institution	Hradec Kralove
Czech Republic	Local Institution	Kladno
Czech Republic	Local Institution	Litomysl
Czech Republic	Local Institution	Mestec Kralove
Czech Republic	Local Institution	Ostrava
Czech Republic	Local Institution	Ostrava Vitkovice
Czech Republic	Local Institution	Praha 1
Czech Republic	Local Institution	Praha 1
Czech Republic	Local Institution	Praha 10
Czech Republic	Local Institution	Praha 2
Czech Republic	Local Institution	Usti Nad Labem
Czech Republic	Local Institution	Usti Nad Orlici
Denmark	Local Institution	Arhus C
Denmark	Local Institution	Hellerup
Denmark	Local Institution	Herning
Denmark	Local Institution	Hilleroed
Denmark	Local Institution	Horsens
Denmark	Local Institution	Naestved
Denmark	Local Institution	Silkeborg
France	Local Institution	Angers
France	Local Institution	Arras
France	Local Institution	Besancon
France	Local Institution	Clamart
France	Local Institution	Clermont-Ferrand Cedex 01
France	Local Institution	Dijon
France	Local Institution	Grenoble Cedex 9
France	Local Institution	Langres Cedex
France	Local Institution	Le Kremlin-Bicetre
France	Local Institution	Lille Cedex
France	Local Institution	Limoges Cedex
France	Local Institution	Nantes
France	Local Institution	Paris
France	Local Institution	Paris
France	Local Institution	Pierre Benite
France	Local Institution	Saint-Priest En Jarez
France	Local Institution	Toulouse cedex 9
France	Local Institution	Vernon
Germany	Local Institution	Berlin
Germany	Local Institution	Berlin
Germany	Local Institution	Berlin
Germany	Local Institution	Berlin
Germany	Local Institution	Bochum
Germany	Local Institution	Cologne
Germany	Local Institution	Dortmund
Germany	Local Institution	Dresden
Germany	Local Institution	Dresden
Germany	Local Institution	Frankfurt
Germany	Local Institution	Gottingen
Germany	Local Institution	Karlsbad
Germany	Local Institution	Ludwigshafen
Germany	Local Institution	Mannheim
Germany	Local Institution	Mannheim
Germany	Local Institution	Munchen
Germany	Local Institution	Munich
Hong Kong	Local Institution	Pokfulman
Hong Kong	Local Institution	Shatin, N.T
Hungary	Local Institution	Budapest
Hungary	Local Institution	Budapest
Hungary	Local Institution	Budapest
Hungary	Local Institution	Gyula
Hungary	Local Institution	Kecskemet
Hungary	Local Institution	Miskolc
Hungary	Local Institution	Mosonmagyarovar
Hungary	Local Institution	Szekesfehervar
Hungary	Local Institution	Zalaegerszeg
India	Local Institution	Ahmedabad	Gujarat
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bangalore
India	Local Institution	Bangalore
India	Local Institution	Bengaluru	Karnataka
India	Local Institution	Chennai	Tamil Nadu
India	Local Institution	Gurgaon	Haryana
India	Local Institution	Hyderabad	Andhra Pradesh
India	Local Institution	Hyderabad	Andhra Pradesh
India	Local Institution	Ludhiana	Tagore Nagar
India	Local Institution	Manipal	Karnataka
India	Local Institution	Mohali	Punjab
India	Local Institution	Pune
India	Local Institution	Pune	Maharashtra
Israel	Local Institution	Afula
Israel	Local Institution	Ashkelon
Israel	Local Institution	Hadera
Israel	Local Institution	Haifa
Israel	Local Institution	Haifa
Israel	Local Institution	Holon
Israel	Local Institution	Jerusalem
Israel	Local Institution	Jerusalem
Israel	Local Institution	Kfar Saba
Israel	Local Institution	Nahariya
Israel	Local Institution	Petach-Tikva
Israel	Local Institution	Rehovot
Israel	Local Institution	Safed
Israel	Local Institution	Tel Aviv
Israel	Local Institution	Tel Hashomer
Israel	Local Institution	Tiberias	Lower Galillee
Italy	Local Institution	Bologna
Italy	Local Institution	Castelfranco Veneto (Tv)
Italy	Local Institution	Chieti Scalo
Italy	Local Institution	Cosenza
Italy	Local Institution	Milano
Italy	Local Institution	Padova
Italy	Local Institution	Palermo
Italy	Local Institution	Pavia
Italy	Local Institution	Piacenza
Italy	Local Institution	Pisa
Italy	Local Institution	Reggio Emilia
Italy	Local Institution	Rome
Italy	Local Institution	Rozzano (Mi)
Italy	Local Institution	San Daniele Del Friuli (Ud)
Italy	Local Institution	Vicenza
Italy	Local Institution	Vittorio Veneto (Tv)
Korea, Republic of	Local Institution	Busan
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Malaysia	Local Institution	Georgetown	Penang
Malaysia	Local Institution	Ipoh	Perak
Malaysia	Local Institution	Kuala Lumpur
Malaysia	Local Institution	Melaka
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Durango
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Leon	Guanajuato
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Tijuana	Baja California
Mexico	Local Institution	Xalapa	Veracruz
Mexico	Local Institution	Zapopan	Jalisco
Mexico	Local Institution	Zapopan	Jalisco
Norway	Local Institution	Alesund
Norway	Local Institution	Fredrikstad
Norway	Local Institution	Gjettum
Norway	Local Institution	Gjovik
Norway	Local Institution	Hamar
Norway	Local Institution	Oslo
Norway	Local Institution	Oslo
Norway	Local Institution	Oslo
Norway	Local Institution	Trondheim
Norway	Local Institution	Tynset
Poland	Local Institution	Bialystok
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Gdansk
Poland	Local Institution	Gdynia
Poland	Local Institution	Lodz
Poland	Local Institution	Lublin
Poland	Local Institution	Lublin
Poland	Local Institution	Poznan
Poland	Local Institution	Przeworsk
Poland	Local Institution	Szczecin
Poland	Local Institution	Warsaw
Poland	Local Institution	Warsawa
Poland	Local Institution	Warszawa
Poland	Local Institution	Wroclaw
Poland	Local Institution	Wroclaw
Portugal	Local Institution	Coimbra
Portugal	Local Institution	Guarda
Portugal	Local Institution	Lisboa
Portugal	Local Institution	Lisboa
Puerto Rico	Local Institution	San Juan
Romania	Local Institution	Baia Mare
Romania	Local Institution	Bucharest
Romania	Local Institution	Bucharest
Romania	Local Institution	Bucharest
Romania	Local Institution	Targu Mures
Russian Federation	Local Institution	Arkhangelsk
Russian Federation	Local Institution	Chelyabinsk
Russian Federation	Local Institution	Kazan
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Novosibirsk
Russian Federation	Local Institution	Rostov-On Don
Russian Federation	Local Institution	Ryazan
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	Saint-Petersburg
Russian Federation	Local Institution	Saint-Petersburg
Russian Federation	Local Institution	Saint-Petersburg
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	St Petersburg
Russian Federation	Local Institution	Yaroslavl
Singapore	Local Institution	Singapore
Singapore	Local Institution	Singapore
Singapore	Local Institution	Singapore
South Africa	Local Institution	Bellville	Western Cape
South Africa	Local Institution	Bioemfontein	Free State
South Africa	Local Institution	Centurion	Gauteng
South Africa	Local Institution	Durban	Kwa Zulu Natal
South Africa	Local Institution	George	Western Cape
South Africa	Local Institution	Parktown	Gauteng
South Africa	Local Institution	Pietermaritzburg	Kwa Zulu Natal
South Africa	Local Institution	Pretoria	Gauteng
South Africa	Local Institution	Somerset West	Western Cape
South Africa	Local Institution	Worcester	Western Cape
Spain	Local Institution	Getafe
Spain	Local Institution	L'Hospitalet De Llobregat
Spain	Local Institution	Leon
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Malaga
Spain	Local Institution	Mourente
Spain	Local Institution	Tarragona
Spain	Local Institution	Torrevieja	Alicante
Ukraine	Local Institution	Chernihiv
Ukraine	Local Institution	Dnipropetrovsk
Ukraine	Local Institution	Donetsk
Ukraine	Local Institution	Ivano-Frankivsk
Ukraine	Local Institution	Ivano-Frankivsk
Ukraine	Local Institution	Kharkiv
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Lviv
Ukraine	Local Institution	Odesa
Ukraine	Local Institution	Ternopil
Ukraine	Local Institution	Vinnytsia
Ukraine	Local Institution	Zaporizhzhia
United Kingdom	Local Institution	Livingston	West Lothian
United States	Pulmonary & Critical Care Services, Pc	Albany	New York
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Atlanta Pulmonary Group	Atlanta	Georgia
United States	Medstar Research Health Institute	Baltimore	Maryland
United States	R Adams Cowley Shock Trauma Center	Baltimore	Maryland
United States	Beaver Medical Group	Banning	California
United States	Bay Pines Va Healthcare Systems	Bay Pines	Florida
United States	Lake Washington Vascular, Pllc	Bellevue	Washington
United States	Alabama Clinical Therapeutics, Llc	Birmingham	Alabama
United States	Daniel G. Lorch, Jr, Md, Cpi	Brandon	Florida
United States	Bridgeport Hospital	Bridgeport	Connecticut
United States	Holston Medical Group	Bristol	Tennessee
United States	Kaleida Health System	Buffalo	New York
United States	Mercury Street Medical Group, Pllc	Butte	Montana
United States	Infectious Disease Of Indiana Psc	Carmel	Indiana
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Research Alliance, Inc.	Clearwater	Florida
United States	Huron Hospital	Cleveland	Ohio
United States	University Of Missouri-Columbia	Columbia	Missouri
United States	Remington Davis Inc.	Columbus	Ohio
United States	Atlanta Institute For Medical Research, Inc	Decatur	Georgia
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Hurley Medical Center	Flint	Michigan
United States	Fort Smith Lung Center	Fort Smith	Arkansas
United States	University Of California San Francisco-Fresno	Fresno	California
United States	New West Physicians	Golden	Colorado
United States	Altru Health System Clinic	Grand Forks	North Dakota
United States	Internal Medical Associates Of Grand Island, P.C	Grand Island	Nebraska
United States	Great Falls Clinic, Llp	Great Falls	Montana
United States	Greenville Hospital System	Greenville	South Carolina
United States	Kentucky Lung Clinic	Hazard	Kentucky
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Primecare Medical Group	Houston	Texas
United States	Kore Cv Research	Jackson	Tennessee
United States	River City Clinical Research	Jacksonville	Florida
United States	Gateway Cardiology. P.C	Jerseyville	Illinois
United States	Veterans Affairs Medical Center	Kansas City	Missouri
United States	Univ. Of Kentucky Dept. Of Surgery	Lexington	Kentucky
United States	University Of Arkansas For Medical Sciences	Little Rock	Arkansas
United States	Horizon Research Group, Inc.	Mobile	Alabama
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Dept Of Internal Med, Sect Of Pulmonary & Critical Care Med	New Haven	Connecticut
United States	West Suburban Medical Center	Oak Park	Illinois
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Research Integrity, Llc	Owensboro	Kentucky
United States	Mississippi Medical Research, Llc	Picayune	Mississippi
United States	Oregon Health Science University	Portland	Oregon
United States	Rex Healthcare	Raleigh	North Carolina
United States	Pen Bay Medical Center	Rockport	Maine
United States	University Of California, Davis Medical Center	Sacramento	California
United States	University Of Utah Medical Center	Salt Lake City	Utah
United States	Cancer Care Centers Of South Texas	San Antonio	Texas
United States	Chest Medicine & Critical Care Medical Gr. Inc.	San Diego	California
United States	Chatham Hospitalists	Savannah	Georgia
United States	Washington University School Of Medicine	St Louis	Missouri
United States	St. John'S Mercy Medical Center	St. Louis	Missouri
United States	Pasadena Center For Medical Research	St. Petersburg	Florida
United States	Stanford University Medical Center	Stanford	California
United States	Richmond University Medical Center	Staten Island	New York
United States	Piedmont Healthcare/Research	Statesville	North Carolina
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Franciscan Research Center	Tacoma	Washington
United States	Tampa Clinical Research	Tampa	Florida
United States	Harbor Ucla Medical Center	Torrance	California
United States	New York Medical College	Valhalla	New York
United States	Office Of Michele S. Maholtz Md	Vero Beach	Florida
United States	George Washington University Medical Faculty Associates	Washington	District of Columbia
United States	Cleveland Clinic Florida	Weston	Florida
United States	Drogue Medical, Llc	Wheat Ridge	Colorado
United States	Wilmington Medical Research	Wilmington	North Carolina
United States	Heartland Vascular Medicine And Surgery	Windsor Heights	Iowa
United States	Clinical Trials Of America, Inc.	Winston Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Chile,  China,  Czech Republic,  Denmark,  France,  Germany,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Norway,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or VTE-Related Death During 6 Months of Treatment	VTE: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All events were adjudicated by an ICAC blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants): n/N (n=number of participants with observation; N=total number of efficacy evaluable participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint: events at any time from randomization until end of intended treatment, regardless whether drug treatment was received. All randomized participants with a non-missing primary endpoint were summarized. Missing endpoint = outcomes which could not be documented on or after study Day 154. Participants were categorized to the assigned group regardless of the treatment actually received (intent-to-treat).	Day 1 to Week 24 + 2 Days or 355 days (Discontinued Early)	Yes
Secondary	Incidence of Adjudicated Composite of Recurrent Symptomatic Venous Thromboembolism (VTE) or All-Cause Death	VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of efficacy evaluable participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received, ie intent to treat (ITT) principle. Each participant scored as having an event only if they experienced one or more of the elements of the composite. Participants with missing endpoint information excluded.	Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or Cardiovascular (CV)-Related Death	VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of efficacy evaluable participants, participants with missing endpoint information excluded). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received, ie, ITT principle. Each participant scored as having an event only if the participant experienced one or more of the elements of the composite.	Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)	No
Secondary	Incidence of Adjudicated Composite of Recurrent Symptomatic VTE or VTE-related Death or Major Bleeding	VTE included: nonfatal DVT or nonfatal PE. All events were adjudicated by an ICAC blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Major bleeding defined by International Society on Thrombosis and Haemostasis: acute, clinically overt bleeding associated with decrease in hemoglobin (Hgb) of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or bleeding that is fatal . Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint and including those not in the efficacy evaluable population with a bleeding event that occurred during treatment period. Events included regardless of whether or not participant received treatment, ie, ITT principle	Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)	No
Secondary	Incidence of Adjudicated Composite of Recurrent Symptomatic VTE, Myocardial Infarction, Stroke, CV-related Death, Clinically Relevant Non-major (CRNM) Bleeding or Major Bleeding	VTE=Nonfatal DVT or nonfatal PE adjudicated by ICAC blinded to treatment. DVT: compression ultrasound and/or venography; PE: spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Major Bleeding = acute, clinically overt bleeding: decrease in Hgb of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or fatal bleeding. CRNM = acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis >5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint and including those not in the efficacy evaluable population with a bleeding event that occurred during treatment period). Events included regardless of whether or not treatment was received (ITT).	Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)	No
Secondary	Incidence of Adjudicated Symptomatic Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period	DVT adjudicated by an ICAC blinded to treatment. DVT evaluated by: compression ultrasound and/or venography. Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication, intent to treat principle (ITT). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early).	Day 1 up to 24 Weeks + 2 Days or 355 Days (Discontinued Early)	No
Secondary	Incidence of Adjudicated Symptomatic Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period	PE adjudicated by an ICAC blinded to treatment. PE: spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication (ITT principle). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early).	Day 1 to Week 24 + + 2 Days or 355 Days (Discontinued Early)	No
Secondary	Incidence of Adjudicated Venous Thromboembolism (VTE)-Related Death During the Intended Treatment Period	VTE-related death included: DVT-related death or PE-related death. All events were adjudicated by an ICAC blinded to treatment. DVT was assessed by compression ultrasound and/or venography; PE was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of participants in respective treatment groups excluding participants with missing endpoint information). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occur during the intended treatment period regardless of whether or not the participant received study medication (ITT principle).	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	No
Secondary	Incidence of Cardiovascular (CV)-Related Death Including VTE-related Death During the Intended Treatment Period	VTE-related death included: DVT-related death or PE-related death. All events were adjudicated by an ICAC blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of participants with observation; N=total number of participants in respective treatment groups excluding participants with missing endpoint information). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occur during the intended treatment period regardless of whether or not the participant received study medication (ITT principle).	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	No
Secondary	Incidence of All-Cause Death During the Intended Treatment Period	Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Includes events that occurred during the intended treatment period, regardless of whether the participant received study medication (ITT principle). Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants, excluding those with missing endpoint information).	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	No
Secondary	Incidence of Adjudicated Major Bleeding During the Treatment Period in Treated Participants	All events were adjudicated by an ICAC blinded to treatment. Bleeding defined by International Society on Thrombosis and Haemostasis: Major Bleeding: acute, clinically overt bleeding: decrease in hemoglobin (hgb) of 2 g/dL or more or bleeding leading to transfusion or bleeding in a critical site or fatal bleeding. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Incidence of Adjudicated Major/CRNM Bleeding During the Treatment Period in Treated Participants	Major Bleeding = acute, clinically overt bleeding: decrease in hemoglobin of 2 g/dL or more, or bleeding leading to transfusion, or bleeding in a critical site, or fatal bleeding. CRNM = acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis >5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. Minor =: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM. All events were adjudicated by an ICAC blinded to treatment. Total bleeding = any of major, or CRNM, or minor bleeding. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of treated (received at least 1 dose of study drug).	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Incidence of Adjudicated Clinically Relevant Non Major (CRNM) Bleeding During the Treatment Period in Treated Participants	Bleeding defined by International Society on Thrombosis and Haemostasis: CRNM defined as acute clinically overt bleeding: compromising hemodynamics, leading to hospitalization, hematoma, epistasis >5 minutes or repetitive, gingival bleeding, hematuria, macroscopic gastrointestinal hemorrhage, rectal blood loss, hemoptysis. All events were adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants with event): calculated as n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Incidence of Adjudicated Minor Bleeding During the Treatment Period in Treated Participants	Bleeding defined by International Society on Thrombosis and Haemostasis: Minor bleeding: all acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM. All events wre adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants) calculated as n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Incidence of Adjudicated Total Bleeding During the Treatment Period in Treated Participants	Bleeding defined by International Society on Thrombosis and Haemostasis: Total Bleeding defined as any of major, CRNM, or minor bleeding. All events were adjudicated by an ICAC blinded to treatment. Event rate (proportion of participants with event): n/N (n=number of participants with observation; N=Total number of participants in respective treatment group (all participants who received at least one dose of study drug). Participants were categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to the treatment received.	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Discontinuations Due to AEs and Death During the Treatment Period in Treated Participants	Treated Participants: all who received at least 1 dose of study drug. Participants categorized to the treatment group to which they were assigned unless incorrect study treatment was received throughout the study, in which case the participant was categorized according to treatment received. Included all SAEs and AEs with onset from first dose to last dose + 2 days (for AEs) or + 30 days (for SAEs); note; bleeding AEs and SAEs from first dose to last dose + 2 days included. Discontinuations due to AE included all AEs/SAEs from first dose until drug was discontinued. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.	First dose to last dose of 24 Weeks + 2 days (AEs) or + 30 days (SAEs) or until drug discontinued	Yes
Secondary	Number of Treated Participants With Marked Abnormalities in Hematology Laboratory Tests	Lower limit of normal (LLN). Upper limit of normal (ULN). Pre-therapy (PreRx). Absolute (Abs) neutrophil count, bands + neutrophils (ANC). Cells per microliter (c/µL). Grams per deciliter (g/dL). Cells per Liter (c/L). Millimeter (MM). White blood cells: < 0.75*LLN, > 1.25*ULN; Hemoglobin: <= 11.5 g/dL (males), <= 9.5 g/dL (females); Hematocrit: <= 37% (males), <= 32% (females); Erythrocytes: <0.75*10^6 c/µL*PreRx; Platelet count: < 75*10^9 c/L, > 700*10^9 c/L; ANC: < 1.00*10^3 c/µL; Abs eosinophils: > 0.750*10^3 c/µL; Abs Basophils: > 400/MM^3; Abs Monocytes> 2000/MM^3; Abs Lymphocytes: < 0.750*10*3 c/ µL, > 7.5*10^3 c/ µL.	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Number of Treated Participants With Marked Abnormalities in Electrolyte Laboratory Tests	Bicarbonate milliequivalents/Liter (mEq/L) Low/High: < 0.75*LLN or > 1.25*ULN, or if pre-dose < LLN then use < 0.75*pre-dose or > ULN if pre-dose > ULN then use > 1.25*pre-dose or < LLN; Serum Calcium mg/dL Low/High: < 0.8*LLN or > 1.2*ULN, or if pre-dose < LLN then use < 0.75*pre-dose or > ULN if pre-dose > ULN then use > 1.25*pre-dose or < LLN; Serum Chloride mEq/L: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use < 0.9*pre-dose or > ULN if pre-dose > ULN then use > 1.1*pre-dose or < LLN; Serum Potassium mEq/L: < 0.9*LLN or > 1.1*ULN, or if pre-dose < LLN then use < 0.9*pre-dose or > ULN if pre-dose > ULN then use > 1.1*pre-dose or < LLN; Serum Sodium mEq/L: < 0.95*LLN or > 1.05*ULN, or if pre-dose < LLN then use < 0.95*pre-dose or > ULN if pre-dose > ULN then use > 1.05*pre-dose or < LLN.	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Number of Treated Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests	Blood urea nitrogen (BUN), milligrams/deciliter (mg/dL), units per liter (U/L). BUN mg/dL High: > 1.5*ULN; Creatinine mg/dL: > 1.5*ULN; Alanine aminotransferase (ALT) U/L: > 3*ULN; Aspartate aminotransferase (AST) U/L: > 3*ULN; Alkaline phosphatase U/L: > 2*ULN; Bilirubin Direct mg/dL: > 1.5*ULN; Bilirubin Total mg/dL: > 2*ULN.	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Number of Treated Participants With Marked Abnormalities in Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests	Creatine kinase High: >5*ULN Units/Liter (U/L); Total Protein High/Low: < 0.9 *LLN or > 1.1*ULN, or if pre-dose < LLN then use 0.9* pre-dose or > ULN if pre-dose > ULN then use 1.1 *pre-dose or	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes
Secondary	Number of Treated Participants With Marked Abnormalities in Urinalysis Laboratory Tests	All tests in urine: Glucose: If missing pre-dose use = 2, or if value = 4, or if pre-dose = 0 or 0.5 use = 2, or if pre-dose = 1 use = 3, or if pre-dose = 2 or 3 use = 4; Protein: If missing pre-dose use = 2, or if value = 4, or if pre-dose = 0 or 0.5 use = 2, or if pre-dose = 1 use = 3, or if pre-dose = 2 or 3 use = 4; Blood: If missing pre-dose use = 2, or if value = 4, or if pre-dose = 0 or 0.5 use = 2, or if pre-dose = 1 use = 3, or if pre-dose = 2 or 3 use = 4; Leukocyte esterase: If missing pre-dose use = 2, or if value = 4, or if pre-dose = 0 or 0.5 use = 2, or if pre-dose = 1 use = 3, or if pre-dose = 2 or 3 use = 4;Red blood cells (RBC): If missing pre-dose use = 2, or if value = 4, or if pre-dose = 0 or 0.5 use = 2, or if pre-dose = 1 use = 3, or if pre-dose = 2 or 3 use = 4; White blood cells (WBC): If missing pre-dose use = 2, or if value = 4, or if pre-dose = 0 or 0.5 use = 2, or if pre-dose = 1 use = 3, or if pre-dose = 2 or 3 use = 4.	Day 1 to Week 24 + 2 Days or 355 Days (Discontinued Early)	Yes

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